title: Protein kinase A and C regulate leak potassium currents in freshly isolated vascular myocytes from the aorta.
abstract: We tested the hypothesis that protein kinase A (PKA) inhibits K2P currents activated by protein kinase C (PKC) in freshly isolated aortic myocytes. PDBu, the PKC agonist, applied extracellularly, increased the amplitude of the K2P currents in the presence of the "cocktail" of K(+) channel blockers. Gö 6976 significantly reduced the increase of the K2P currents by PDBu suggesting the involvement of either α or β isoenzymes of PKC. We found that forskolin, or membrane permeable cAMP, did not inhibit K2P currents activated by the PKC. However, when PKA agonists were added prior to PDBu, they produced a strong decrease in the K2P current amplitudes activated by PKC. Inhibition of PDBu-elicited K2P currents by cAMP agonists was not prevented by the treatment of vascular smooth muscle cells with PKA antagonists (H-89 and Rp-cAMPs). Zn(2+) and Hg(2+) inhibited K2P currents in one population of cells, produced biphasic responses in another population, and increased the amplitude of the PDBu-elicited K(+) currents in a third population of myocytes, suggesting expression of several K2P channel types. We found that cAMP agonists inhibited biphasic responses and increase of amplitude of the PDBu-elicited K2P currents produced by Zn(2+) and Hg(2). 6-Bnz-cAMp produced a significantly altered pH sensitivity of PDBu-elicited K2P-currents, suggesting the inhibition of alkaline-activated K2P-currents. These results indicate that 6-Bnz-cAMP and other cAMP analogs may inhibit K2P currents through a PKA-independent mechanism. cAMP analogs may interact with unidentified proteins involved in K2P channel regulation. This novel cellular mechanism could provide insights into the interplay between PKC and PKA pathways that regulate vascular tone.
authors.affiliation: Department of Pharmacology and Toxicology, Michigan State University, East Lansing, Michigan, United States of America ; Department of Pharmacology, Universidad Central Del Caribe, Bayamon, Puerto Rico, United States of America.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Hayoz
authors.forename: Luis
authors.initials: L
authors.lastname: Cubano
authors.forename: Hector
authors.initials: H
authors.lastname: Maldonado
authors.forename: Rostislav
authors.initials: R
authors.lastname: Bychkov
mesh_terms: D000818:Animals; D001011:Aorta / Q000166:cytology*; D002469:Cell Separation; D000242:Cyclic AMP / Q000819:agonists / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D015640:Ion Channel Gating / Q000187:drug effects; D008628:Mercury / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D032342:Muscle Cells / Q000187:drug effects / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D015032:Zinc / Q000494:pharmacology
chemical_list: D026902:Potassium Channel Blockers; D015221:Potassium Channels; D015240:Phorbol 12,13-Dibutyrate; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D008628:Mercury; D015032:Zinc